Fan, Tian-Yun published the artcileStructure-activity relationship and biological evaluation of berberine derivatives as PCSK9 down-regulating agents, Recommanded Product: 2-Methoxy-4-(2-nitroethyl)phenol, the publication is Bioorganic Chemistry (2021), 104994, database is CAplus and MEDLINE.
Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a secreted protein and its deficiency markedly enhances the survival rate of patients with cardiovascular diseases (CVDs). Forty berberine (BBR) derivatives I (R1 = H, MeO, R2 = MeO, OH, PhCH2O, EtO, R3 = MeO, OH, EtO, R2R3 = OCH2O, R4 = H, MeO, R5 = H, Cl, MeO, PhCH2O, cyclobutylmethoxy, etc., R6 = MeO, OH, R7 = MeO, EtO, H) were synthesized and evaluated for their activity on down-regulating the transcription of PCSK9 in HepG2 cells, taking BBR as the lead. Structure-activity relationship (SAR) anal. revealed that the 2,3-dimethoxy moiety might be beneficial for activity. Among them, I (R1 = R4 = R7 = H, R2 = R3 = R6 = MeO, R5 = p-F3CSC6H4CH2O) (II) displayed the most potent activity with an IC50 value of 9.5 ± 0.5μM, better than that of BBR. Also, it significantly decreased the PCSK9 protein level at the cellular level, as well as in the liver and serum of mice in vivo. Furthermore, II markedly increased LDLR expression and LDL-C clearance via down-regulating PCSK9 protein. The mechanism of action of II is targeting HNF1α and/or Sp1 cluster modulation upstream of PCSK9, a different one from BBR. Therefore, II might have the potential to be a novel PCSK9 transcriptional inhibitor for the treatment of atherosclerosis, worthy for further investigation.
Bioorganic Chemistry published new progress about 528594-30-1. 528594-30-1 belongs to alcohols-buliding-blocks, auxiliary class Nitro Compound,Benzene,Phenol,Ether, name is 2-Methoxy-4-(2-nitroethyl)phenol, and the molecular formula is C9H11NO4, Recommanded Product: 2-Methoxy-4-(2-nitroethyl)phenol.
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